Increased Hyaluronan and Hyaluronidase Production and Hyaluronan Degradation in Injured Aorta of Insulin-Resistant Rats

Abstract

Abstract —Diabetic patients have a greater incidence of restenosis, which has been shown to be related to exaggerated intimal hyperplasia. Hyaluronan (HA) has been shown to be closely involved in arterial smooth muscle cell proliferation and migration, which provoke intimal hyperplasia after balloon catheter injury. Our aim was to determine the effect of fructose feeding, which produces certain characteristics of non–insulin-dependent diabetes (ie, insulin resistance, hyperinsulinemia, and hypertriglyceridemia), on production of HA and hyaluronidase and degradation of HA in rat aorta. Treated rats received fructose (25% in tap water) 12 weeks before balloon catheter injury and 14 days afterward. Fructose-fed rats had hyperinsulinemia and hypertriglyceridemia. Injury increased intima-media wet weight (7.5%) and DNA content (20%) in control rats. This increase was significantly greater in fructose-fed rats (22% for wet weight and 34% for DNA content) and was associated with greater HA and hyaluronidase production (123% and 41%, respectively) than in control rats (49% and 7%, respectively). Determination of HA molecular mass showed that balloon catheter injury increased the number of HA fragments in the aorta of control rats. Normal aorta of fructose-fed rats contained more HA fragments than that of control rats. Injury to the aorta of fructose-fed rats increased HA fragments and induced the appearance of a very-high-molecular-mass (>2000 kDa) HA. In conclusion, fructose treatment, which induced hyperinsulinemia and hypertriglyceridemia, increased HA and hyaluronidase production and HA degradation in injured aorta. This finding suggests that HA, which has been shown to play a crucial role in proliferation and migration of arterial smooth muscle cells, may be involved in the promotional effect of long-term fructose feeding on arterial wall reaction to injury.